All over the world, pre-menopausal women are dreading -that time of the month' which they call -the curse' because of the sometimes dreadful symptoms that occur. Roughly 75% of women are believed to experience PMS (premenstrual syndrome) and about half of those have symptoms that are severe enough to interfere with their daily life. A psychiatric condition known as premenstrual dysphoric disorder affects 3% of women with PMS. Symptoms include anxiety and irritability, headaches, joint and breast pain which usually strikes a week before the onset of menses.
For serious cases, the doctor may prescribe a combined contraceptive pill, which if taken continuously may stabilize hormone levels. A diuretic may relieve bloating and tender breasts. You might even be offered psychological help in the form of short term cognitive behavioural therapy and stress management. And the -final solution', a hysterectomy.
Some medicos believe that PMS is an exaggerated response to stress triggered by withdrawal effects as the secretions of ovarian hormones declines. Stimuli that would not normally be upsetting may trigger aberrant responses during the premenstrual period. Recent research has now identified an organic cause for the condition and importantly, a solution. Thelma Lovick, a neuroscientist at Birmingham University in England has been researching the cause of PMS and the underlying neuronal mechanism. The Medical Research Council has provided funding for this three year study and Lovick. Based on her work on female rats, which also show a change in behaviour during their cycle, she has found that a widely used antidepressant, Prozac, has the ability to raise brain levels of a steroid compound called allopregnanolone, ALLO for short, and believes this property could be exploited to stop pre-menstrual-like symptoms in rats.
In women, premenstrual symptoms appear when progesterone levels fall at the end of the menstrual cycle. 'Progesterone is a hormone that circulates in the bloodstream and gets into the brain," said Lovick. 'It breaks down to ALLO, and it's this rapid change in the ALLO concentration in the brain that causes increased excitability in the nerve circuits in parts of the brain that are involved in emotional behaviour." She went on to explain 'ALLO can alter the activity of nerve cells, thus it is described as a neuroactive steroid. ALLO normally produces calming effects. It enhances the activity of GABA, one of the brain's inhibitory neurotransmitter chemicals, in those parts of the brain that process emotional responses".
As progesterone levels, and therefore ALLO levels drop just before completion of the menstrual cycle, the natural inhibition gets turned off. 'As a consequence, these brain circuits become more excitable, leaving the individual more responsive to stress, which is often manifested behaviourally as anxiety and aggression."
Lovick knew that the widely used antidepressant fluoxtetine (commonly known as Prozac) could raise the concentration of ALLO levels in the brain. She predicted that if fluoxetine was taken at the time that ALLO levels were falling sharply during the premenstrual period, the brain concentration would decline much more slowly than normal and PMS may not develop. 'Millions of women take Prozac for depression but the dose they take is relatively high. One of the effects of fluoxetine is that it acts on serotonin systems in the brain, that's why it's used as an antidepressant. One of the things it does in addition, is to increase ALLO concentrations in the brain and it does this at very low doses." The breakthrough is the realization that to treat PMS, only very low doses would be needed and the drug would be taken only during the premenstrual period...
'We've got available to us a drug that is already in production, it's already gone through its safety tests, something we could use at very low dose to perhaps ameliorate the development of pre-menstrual syndrome in women," said Lovick at a presentation a the British Science Festival in mid-September.
Just before women suffering severe PMS symptoms rush off to the doctor, Tim Kendall, from the Royal College of Psychiatrists, warns that Prozac has side effects, most commonly sexual dysfunction, with lowered libido and impotence. It can also affect the appetite, stop you sleeping and promote anxiety. It has also been known to trigger thoughts of suicide in younger people. However he was uncertain whether these side effects would occur with low doses that Lovick believes should be effective for PMS.
The standard dose of 10-20 mg a day has sometimes been prescribed for PMS treatment but normally it is used as an antidepressant. Lovick said that only one tenth of a dose normally prescribed should produce an effect on brain ALLO levels. 'And you'd be taking it for about a week so that the side-effect issue should be non-existent," she added.
The next step is clinical trials.
- Gloria Burley
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